IDEAYA Highlights Results for GSK-Approved MAT2A Inhibitor

Shares of IDEAYA Biosciences surged nearly 15% on Monday following the release of encouraging Phase II data for IDE397, a novel MAT2A inhibitor designed for treating solid tumors. The study primarily targeted patients with urothelial and non-small-cell lung cancer (NSCLC) who possess an MTAP gene deletion. The results showed a 39% overall response rate (ORR), affirming IDEAYA's decision to continue with the drug despite GSK's decision to exit the program.

The MTAP gene acts as a tumor suppressor, and its deletion makes cancer cells reliant on the enzyme MAT2A, which is essential for producing a critical compound needed for cellular functions. IDE397 leverages this weakness in tumors deficient in MTAP.

In the study, which included 18 evaluable patients who had previously undergone a median of two treatment lines, IDEAYA reported one complete response (CR) and six partial responses (PRs), with two PRs still pending confirmation. As of the June 21 cutoff date, five of the seven responding patients continued to show positive outcomes. Additionally, the disease control rate (DCR) was reported at 94%, with 14 out of the 18 patients (78%) experiencing tumor shrinkage. The study also noted an 81% molecular response rate in circulating tumor DNA (ctDNA), with 13 out of 16 patients showing at least a 50% reduction in ctDNA. Median progression-free survival has not yet been determined.

IDEAYA's CEO, Yujiro Hata, emphasized the significance of these findings, describing them as "important clinical proof-of-concept in MTAP-deletion solid tumors" and highlighting the "encouraging preliminary durability" of the drug, which is administered as a convenient 30mg once-daily tablet.

Regarding safety, 5.6% of patients experienced Grade ≥3 drug-related adverse events (AEs), but there were no reports of drug-related serious events or discontinuations. IDEAYA believes that the favorable adverse event profile and dosing convenience could allow for long-term dosing and potential development of combination therapies.

Mizuho Securities analyst Graig Suvannavejh projects peak sales of $1.2 billion for IDEAYA in MTAP-deleted cancers.

IDEAYA and GSK had initially formed a partnership in 2020 to focus on synthetic lethality, covering three of IDEAYA's programs: MAT2A, Pol Theta, and Werner Helicase. However, GSK terminated its research on the MAT2A inhibitor, also known as GSK4362676, in 2022. Research on the other two programs is still ongoing.

In addition to the current monotherapy trial, IDEAYA is exploring combination strategies for IDE397. The drug is currently undergoing Phase I/II testing together with Amgen's second-generation PRMT5 inhibitor AMG 193 in NSCLC patients, with an expected completion date in 2026. Furthermore, it is part of a Phase I study in combination with Gilead Sciences' Trop-2-directed antibody-drug conjugate, Trodelvy (sacituzumab govitecan).